Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection.

ABSTRACT: HCV infection can decrease NAD⁺/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O^Tg mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7.5.1 cells. Furthermore, QPRT enzymatic activity involved in suppression of HCV replication in cells. Activation of QPRT with clofibrate (CLO) or addition of

SUBMITTER: Wang Z 

PROVIDER: S-EPMC5517448 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature